Several of this month's articles and interviews touch on themes that relate to spectrum phenomena as well as the Diagnostic and Statistical Manual of Mental Disorders developmental process.

First, Darrel A. Regier, MD, MPH, director of the Division of Research at American Psychiatric Association, discusses, in an interview with CNS Spectrums, the developmental process for DSM-V. He emphasizes the use of dimensional measures to determine both thresholds for disorders, and to assess response to treatments. He also highlights a focus on spectra of disorders that cut across traditional diagnostic boundaries as one way to deal with issues of comorbidity. Finally, he discusses new approaches to the five DSM axes, and the need to link together the DSM and International Classification of Diseases processes. Three other articles in this issue also clearly relate to these obsessive-compulsive spectra issues.

For example, Leonardo F. Fontenelle, MD, PhD, describes how, although much attention has been paid to patients who lack insight into their obsessional beliefs, less importance has been given to individuals with obsessive-compulsive disorder (OCD) who display perceptual disturbances typically found in psychotic disorders, including schizophrenia, schizoaffective disorders, or mood disorders with psychotic features. The authors call attention to a phenomenon that has been neglected in the psychiatric literature (ie, the occurrence of hallucinations and related phenomena in patients with OCD). They describe five patients with OCD with hallucinations in several different sensory modalities, including the auditory, the visual, the tactile, the olfactory, and the cenesthetic modalities, and suggest that further psychopathological research should clarify the clinical significance of hallucinations among patients with OCD.

Personalizing medicine by understanding the unique properties of each patient's genome has the potential of predicting what drug to prescribe for that individual. This approach has already proven useful for several drugs in medicine and promises to become a strategy for selection of therapeutics in psychiatry soon. Understanding some of the key concepts, strategies, and advances in the field of pharmacogenomics can set the stage for adapting emerging findings to the practice of psychopharmacology.

Although much attention has been paid to patients who lack insight into their obsessional beliefs, less importance has been given to individuals with obsessive-compulsive disorder (OCD) who display perceptual disturbances typically found in psychotic disorders, including schizophrenia, schizoaffective disorders, or mood disorders with psychotic features. We would like to call the attention to a phenomenon that has been neglected in the psychiatric literature: the occurrence of hallucinations and related phenomena in patients with OCD. In this case report, we describe five clinical vignettes of patients with OCD with hallucinations in several different sensory modalities, including the auditory, the visual, the tactile, the olfactory, and the cenesthetic ones. Further psychopathological research should clarify the clinical significance of hallucinations among patients with OCD.

Diphenhydramine is a widely used antihistaminic that is frequently included in over-the-counter medications. Due to its sedating properties, diphenhydramine is used in some hypnotic preparations. Occasionally, patients respond to diphenhydramine with paradoxical excitation. There are no studies on the prevalence of paradoxical excitation in healthy subjects. Diphenhydramine appears to cause mild inhibition of the cytochrome P450 (CYP) 2D6 enzyme. This can be interpreted as competitive inhibition, suggesting that diphenhydramine may be a CYP2D6 substrate. When subjects have at least three active copies of the CYP2D6 gene, they are called ultrarapid metabolizers (UMs) and present high metabolic capacity for CYP2D6 substrates. In the United States, CYP2D6 UMs may account for ∼1 % to 2% of the population. We describe three CYP2D6 UMs who reported paradoxical excitation on diphenhydramine. These cases suggest that in CYP2D6 UMs, diphenhydramine may be converted to a compound that causes excitation due to the abnormally high CYP2D6 activity. Therefore, such individuals may be at higher risk for excitation. Although these are onl y three anecdotal cases of paradoxical excitation from three CYP2D6 UMs, the reports illustrate the need for larger, more formal studies of diphenhydramine responses in CYP2D6 UMs and of diphenhydramine metabolism.